Volume 27, Issue 12, Pages R580-R586 (June 2017) The insular cortex  Nadine Gogolla  Current Biology  Volume 27, Issue 12, Pages R580-R586 (June 2017) DOI: 10.1016/j.cub.2017.05.010 Copyright © 2017 Elsevier Ltd Terms and Conditions

Figure 1 Location of the insular cortex in the human and mouse brain. (A) Anatomy of the human brain. Top left: the insula is folded below the lateral sulcus and is hidden by the opercula (shaded area) of the frontal, parietal and temporal lobes. Top right: when temporal and parietal lobes are pushed aside, the underlying insula can be seen; it is separated into an anterior and posterior part by the central insular sulcus. Bottom: coronal (1) and horizontal (2) cross sections of the human brain reveal the position of the insular cortex (red). (B) Top left: in the mouse, the insula lies exposed on the lateral surface of the brain above the rhinal fissure. The medial cerebral artery (MCA) crosses the insula. Top right: subdivisions and neighboring cortical regions of the mouse insula. AI, agranular insular cortex; AID, agranular insular cortex, dorsal part; AIV, agranular insular cortex, ventral part; AIP, agranular insular cortex, posterior part; DI, dysgranular insular cortex; GI, granular insular cortex. Bottom: coronal cross sections at different levels reveal the location and layers of the mouse insular cortex. Current Biology 2017 27, R580-R586DOI: (10.1016/j.cub.2017.05.010) Copyright © 2017 Elsevier Ltd Terms and Conditions

Figure 2 Connectivity of the insular cortex. A simplified scheme of the basic insula connectivity visualized on the rodent brain. The insular bears reciprocal connections (grey arrows) with sensory, emotional, motivational and cognitive systems and receives strong neuromodulatory input (black arrows) in the+ form of cholinergic afferents from the basal nucleus (BN), dopaminergic input from the ventral tegmental area (VTA), serotonergic input from the raphe nuclei (RN), and adrenergic input from the locus coeruleus (LC). Abbreviations: ACC, anterior cingulate cortex; Amy, amygdala; BNST, bed nucleus of the stria terminalis; Hb, habenula; Hyp, hypothalamus; mPFC, medial prefrontal cortex; NAc, nucleus accumbens; OFC, orbitofrontal cortex; PAG, periaqueductal grey; PBN, parabrachial nucleus; PH, parahippocampus. Current Biology 2017 27, R580-R586DOI: (10.1016/j.cub.2017.05.010) Copyright © 2017 Elsevier Ltd Terms and Conditions

Figure 3 Illustration of an integrated model of insular cortex functions. A schematic model of how diverse insular functions and computations may interact exemplified in the context of a social encounter. (1) The insula cortex receives multisensory information. In this example, it reacts to hearing or seeing people. (2) It processes the salience of incoming stimuli, that is, it responds more to the known (red silhouette) than to the unknown persons (grey silhouettes). (3) The insula assesses the valence of the stimulus, for example, is this a loved or dreaded person, by (4) integrating information from multiple brain systems, including emotional feelings for the person and cognitive information, for example what is known about the person. The insula also perceives (5) bodily feelings and (6) contributes directly to physical reactions caused by the social encounter, e.g. an increase in heartbeat or the feeling of butterflies in the stomach. (7) Through its interactions with other large-scale brain networks, the insula (8) assesses the risk of an interaction by (9) predicting the possible outcomes, i.e. acceptance or rejection. (10) Bodily feelings as well as cognitive processes, e.g. imagination of the outcome, may cause emotions like the pleasure or fear to interact. (11) The uncertainty of the other person’s reaction engages the insula in deciding what to do next. Upon a decision, the insula anticipates the outcome (12) and (13) influences the behavior of seeking or avoiding the contact. Current Biology 2017 27, R580-R586DOI: (10.1016/j.cub.2017.05.010) Copyright © 2017 Elsevier Ltd Terms and Conditions